樟腦磺醯胺衍生之胺化合物與樟腦磺醯胺衍生之羥脯醯胺化合物在催化不對稱加成反應之研究

The Study on Asymmetric Addition Reaction Catalyzed by Camphorsulfonamide-derived-amine and Pyrrolidine–camphorsulfonamide Derivatives

黃昱超(Yu-Chao Huang)

指導教授 ： 汪炳鈞

國立清華大學/理學院/化學系/博士(2014年)

摘要

本論文的目的在於探討樟腦衍生之掌性有機催化劑應用於催化不對稱加成反應。論文共分為三個部分，第一部份我們利用便宜的樟腦磺酸為起始物，經由四個反應步驟而得到新型一級胺催化劑42，並以催化劑42(10 mol%)、對硝基苯甲酸(20 mol%)、5當量的水，以異丙醇為反應溶劑在28度c，催化2,2-二甲基-1,3-二氧陸圜-5-酮 (1,3-dioxan-5-one)加成至醛類化合物的不對稱醛醇反應，可得到高達96% 鏡像選擇性的加成產物及最高4:96的非鏡像選擇性(anti:syn)。
第二部份在探討開發新型的樟腦磺酸衍生之羥脯醯胺54b作為有機催化劑催化2,2-二甲基-1,3-二氧陸圜-5-酮和beta-硝基烯類的不對稱1,4-加成反應。在10 mol%的催化劑54b搭配5 mol%的2,4-二硝基苯酚和5當量的水以甲苯為溶劑，在20度c進行反應，可得到加成產物，產率最高可達93%，及最高91:9的非鏡像選擇性(syn:anti)及高達94%的鏡像選擇性。
第三部份我們利用單取代磺醯胺催化劑30催化硝基烷類與alpha,beta-不飽和醛的不對稱1,4-加成反應。而催化劑30的優點在於它只須要1-2 mol%的催化量以及不需額外添加任何酸或是鹼的條件下，即可得到最高有99% ee的加成產物。

關鍵字

有機催化反應 ； 不對稱加成反應 ； 有機催化劑 ； 樟腦磺酸

並列摘要

This thesis deals with the application of camphor-derived organocatalyst in asymmetric addition reaction. The fisrt part discusses the asymmetric aldol reaction of 2,2-dimethyl-1,3-dioxan-5-one with aldehydes in the presence of 10 mol% organocatalyst 42 and 20 mol% p-nitrobenzoic acid to give aldol products in good yields with high enatio- and diastereoselectivities. (up to 99% ee, 4:96 dr)
The second part deals with the development of camphorsulfonamdie-derived (2S,4R)-4-hydroxy-L-prolinamide 54b as organocatalyst. Catalyst 54b is able to catalyze asymmetric Michael addition of 2,2-dimethyl-1,3-dioxan-5-one to nitro alkenes. The asymmetric reaction could give γ-nitro-dihydroxyacetones in good yields with high enatio- and diastereoselectivities (up to 94% ee, 91:9 dr) in the presence of 10 mol% organocatalyst 54b, 5 mol% 2,4-dinitrophenol and 5 equiv. of water in toluene.
The third part discusses pyrrolidine-camphorsulfonamide based catalyst 30 in the asymmetric catalytic Michael addition reaction of nitroalkanes to alpha,beta-unsaturated aldehydes without the addition of acid additive to produce desired products with up to 99% ee and good yields. The main advantage of this catalyst is high efficiency and enantioselectivity with low catalytic loading (1-2 mol%). These remarkable advantages make this approach very suitable for gram-scale synthetic use.

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